Variant chr10-24584454-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020824.4(ARHGAP21):c.5835T>A(p.Ser1945=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,613,462 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

ARHGAP21
NM_020824.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.990

Variant links:

Genes affected

ARHGAP21 (HGNC:23725): (Rho GTPase activating protein 21) ARHGAP21 functions preferentially as a GTPase-activating protein (GAP) for CDC42 (MIM 116952) and regulates the ARP2/3 complex (MIM 604221) and F-actin dynamics at the Golgi through control of CDC42 activity (Dubois et al., 2005 [PubMed 15793564]).[supplied by OMIM, Mar 2008]

ARHGAP21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-24584454-A-T is Benign according to our data. Variant chr10-24584454-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640350.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.99 with no splicing effect.

BS2

High AC in GnomAd4 at 399 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP21	NM_020824.4 linkuse as main transcript	c.5835T>A	p.Ser1945=	synonymous_variant	26/26	ENST00000396432.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP21	ENST00000396432.7 linkuse as main transcript	c.5835T>A	p.Ser1945=	synonymous_variant	26/26	1	NM_020824.4	A2	Q5T5U3-1

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

394

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00307

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00282

AC:

706

AN:

250366

Hom.:

AF XY:

0.00265

AC XY:

358

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.000898

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000885

Gnomad FIN exome

AF:

0.000881

Gnomad NFE exome

AF:

0.00348

Gnomad OTH exome

AF:

0.00639

GnomAD4 exome

AF:

0.00318

AC:

4647

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

2299

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.00275

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.00104

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.000899

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00360

GnomAD4 genome

AF:

0.00262

AC:

399

AN:

152230

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00321

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00307

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00330

Hom.:

Bravo

AF:

0.00310

EpiCase

AF:

0.00453

EpiControl

AF:

0.00510

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ARHGAP21: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.15

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over